PMID- 21895877 OWN - NLM STAT- MEDLINE DCOM- 20120213 LR - 20131121 IS - 1365-2982 (Electronic) IS - 1350-1925 (Linking) VI - 23 IP - 11 DP - 2011 Nov TI - Persistent epithelial barrier alterations in a rat model of postinfectious gut dysfunction. PG - e523-33 LID - 10.1111/j.1365-2982.2011.01777.x [doi] AB - BACKGROUND: Mucosal mast cells (MMCs), epithelial barrier function (EBF) and the enteric nervous system (ENS) are interactive factors in the pathophysiology of functional gastrointestinal disorders. We characterized postinfectious EBF alterations in the Trichinella spiralis infection model of MMC-dependent intestinal dysfunction in rats. METHODS: Sprague-Dawley rats were infected with T. spiralis. 30 +/- 2 days postinfection, jejunal EBF (electrophysiological parameters, fluorescein isothiocyanate-dextran fluxes and responses to secretagogues and MMC degranulators) was evaluated (Ussing chamber). In some experiments, participation of secretomotor neurons was examined by tetrodotoxin (TTX) pretreatment. Jejunal histology and MMC count and activity were also assessed. KEY RESULTS: 30 +/- 2 days postinfection, when only a low grade inflammation was observed, increased MMC number and activity were associated with altered EBF. EBF alterations were characterized by increased mucosal permeability and ion secretion. In T. spiralis-infected animals, secretory responses to serotonin (5-HT) and immunoglobulin E (IgE)-dependent activation of MMCs were reduced. In contrast, responses to substance P (SP) and capsaicin were similar in infected and noninfected animals. Neuronal blockade with TTX altered secretory responses to SP and capsaicin only in infected rats. CONCLUSIONS & INFERENCES: Trichinella spiralis infection in rats, at late stages, results in persistent postinfectious intestinal barrier dysfunctions and mucosal mastocytosis, with other signs suggestive of a low grade inflammation. The altered permeability and the TTX-independent hyporesponsiveness to 5-HT and IgE indicate epithelial alterations. Changes in responses to SP and capsaicin after neuronal blockade suggest an ENS remodeling during this phase. Similar long-lasting neuro-epithelial alterations might contribute to the pathophysiology of functional and postinfectious gastrointestinal disorders. CI - (c) 2011 Blackwell Publishing Ltd. FAU - Fernandez-Blanco, J A AU - Fernandez-Blanco JA AD - Department of Cell Biology, Physiology and Immunology, Veterinary School, Universidad Autonoma de Barcelona, Barcelona, Spain. FAU - Barbosa, S AU - Barbosa S FAU - Sanchez de Medina, F AU - Sanchez de Medina F FAU - Martinez, V AU - Martinez V FAU - Vergara, P AU - Vergara P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110905 PL - England TA - Neurogastroenterol Motil JT - Neurogastroenterology and motility JID - 9432572 RN - 0 (Neurotransmitter Agents) RN - 0 (Sensory System Agents) RN - 0 (Sodium Channel Blockers) RN - 33507-63-0 (Substance P) RN - 4368-28-9 (Tetrodotoxin) RN - EC 3.4.21.- (chymase 2) RN - EC 3.4.21.39 (Chymases) RN - S07O44R1ZM (Capsaicin) SB - IM MH - Animals MH - Capsaicin/pharmacology MH - Chymases/metabolism MH - Enteric Nervous System/drug effects/pathology/physiopathology MH - Gastrointestinal Tract/microbiology/pathology/physiopathology MH - Inflammation/etiology/pathology/physiopathology MH - Intestinal Mucosa/innervation/*microbiology/*pathology/*physiopathology MH - Ion Transport/physiology MH - Male MH - Mast Cells/cytology/enzymology/microbiology/pathology MH - Mastocytosis/etiology/pathology/physiopathology MH - Neurotransmitter Agents/pharmacology MH - Permeability MH - Rats MH - Rats, Sprague-Dawley MH - Sensory System Agents/pharmacology MH - Sodium Channel Blockers/pharmacology MH - Substance P/pharmacology MH - Tetrodotoxin/pharmacology MH - Trichinella spiralis/pathogenicity MH - Trichinellosis/complications/*pathology/*physiopathology EDAT- 2011/09/08 06:00 MHDA- 2012/02/14 06:00 CRDT- 2011/09/08 06:00 PHST- 2011/09/08 06:00 [entrez] PHST- 2011/09/08 06:00 [pubmed] PHST- 2012/02/14 06:00 [medline] AID - 10.1111/j.1365-2982.2011.01777.x [doi] PST - ppublish SO - Neurogastroenterol Motil. 2011 Nov;23(11):e523-33. doi: 10.1111/j.1365-2982.2011.01777.x. Epub 2011 Sep 5.